Medical overview and Epidemiology

Wilson's disease develops as a consequence of an abnormality in the metabolism of copper that leads to an accumulation of copper in the hepatocytes, eventually leading to cell death. As these cells die, copper is released into the bloodstream and begins to accumulate in the brain, eyes, kidneys, muscles, bones, and joints. It is the accumulation of copper in the brain and liver that creates the most characteristic symptoms of Wilson's disease. The disorder has a broad range of symptoms and requires a high index of suspicion for an accurate diagnosis. Liver disease is the most common presentation in adolescence, with elevated serum aminotransferase levels, jaundice, anorexia, vomiting, abdominal pain, ascites, weight loss, bleeding, hepatomegaly, and splenomegaly. Pediatric patients may present with hemolytic anemia, a disorder with a mortality rate of nearly 80%, and can have a fluctuating course with spon taneous remissions and exacerbations. More than 30% of young patients experience neurological symptoms including dysarthria, dysphagia, and a variety of movement disorders that include dystonia, rigidity, tremor, ataxia, and ballism. Patients may also present with premature osteoporosis and arthritis, cardiomyopathy, pancreatitis, nephrolithiasis, hypoparathyroidism, and infertility. Laboratory studies have noted a low ceruloplasmin in up to 95% of the cases, although the level can be low in asymptomatic cases, and a high 24-hour urine copper level. In half of patients with liver disease and in nearly all patients with neurological or psychiatric symptoms, patients will have Kayser-Fleischer rings on slit-lamp examination. A liver biopsy is another option when the diagnosis is uncertain or when measuring copper concentration. Neuroimaging is recommended in cases with neurological and psychiatric symptoms and frequently demonstrates an increased T2-weighted signal in the caudate, putamen, subcortical white matter, and brain stem.

Penicillamine is the first oral agent used to treat Wilson's disease by producing the excretion of copper in the urine. Tetrathiomolybdate is a more effective chelating agent with fewer side effects, including a much lower risk of neurological deterioration. Trientine is typically used as a chelating agent in cases of hepatic or neuropsychiatric symptoms. Patients with mild to moderate disease recover over a period of 6 months with acute therapy. Any persistent neurological, psychiatric, or hepatic disorder that remains after 2 years is likely to be permanent. A study by Akil et al. (1991) described a good prognosis in nearly two-thirds of patients treated for psychiatric disorders.